Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most prevalent insect-borne disease in the United States. Lyme disease has at least four ominous features. First, it is extremely difficult to diagnose, allowing many infections to go unrecognized and untreated. Second, in contrast to other bacterial infections, the human immune system cannot ward off an untreated infection by B. burgdorferi, thereby leading to a chronic disease state. Third, the clinical consequences of Lyme disease are devastating, manifesting as many debilitating forms such as arthritis, muscle aches, atrioventricular heart block (arrhythmia), and neurological impairments.
B. burgdorferiis exceedingly difficult to study. Part of this difficulty derives from the fact that the bacterium lives half of its life in ticks, and the other half in small mammals (mostly wild mice). The parasitic strategy and life cycle ofB. burgdorferiare very complex. Because the organism occupies two very different environments, it is essential that it drastically alter its physiology to accommodate these diverse niches. Several years ago, we discovered the first regulatory pathway (the RpoN-RpoS pathway) controlling gene expression in the Lyme disease spirochete. This regulatory pathway governs the expression of several of the causative agent’s virulence traits. By further studying the regulation of expression of these virulence-associated molecules, we are making progress towards understanding how the organism maintains itself in nature in both ticks and mammals — including humans.
Using other genetic approaches, we also have discovered several previously unrecognized molecules of B. burgdorferi that may serve as new Lyme disease vaccine candidates. These candidate vaccines are being evaluated in an experimental mouse model of Lyme disease. Finally, we recently discovered a new molecule that plays a major, but unanticipated, role in conferring pathogenicity to the organism; this knowledge has spawned a new avenue of investigation that is likely to uncover other new aspects about the virulence of B. burgdorferi.